A novel human 3D steatohepatitis model recapitulating disease progression for evaluating the efficacy and mechanism of action of MASH therapeutics

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A newly developed human 3D mini-liver disease model successfully recapitulates the pathology and progression of metabolic dysfunction-associated steatohepatitis (MASH) and enables the in vitro evaluation of therapeutic efficacy and mechanisms of action. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Toshihiko Maekawa; Ayu Inoue

doi:10.1254/fpj.26027

August 31, 2026Folia Pharmacologica Japonica

A novel human 3D steatohepatitis model recapitulating disease progression for evaluating the efficacy and mechanism of action of MASH therapeutics

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Key Points

To establish a human three-dimensional steatohepatitis model that recapitulates disease progression for evaluating the efficacy and mechanism of action of therapeutics targeting metabolic dysfunction-associated steatohepatitis (MASH).
Co-cultured primary human hepatocytes and hepatic stellate cells within a functional 3D cell device to construct healthy and disease-state miniature liver models.
Induced fibrosis and characterized disease phenotypes using lipid accumulation assays, fiber deposition assessments, and comprehensive gene expression profiling.
Treated the fibrotic 3D liver model with clinical-stage MASH drug candidates for 1 to 2 weeks to evaluate stellate cell activation markers, collagen production, and fiber deposition.
The 3D disease model demonstrated progressive neutral lipid accumulation, collagen deposition, and sequential upregulation of genes related to oxidative stress, inflammation, and hepatic stellate cell activation.
Treatment with MASH drug candidates effectively altered stellate cell activation and reduced collagen synthesis and fiber deposition, validating the model for therapeutic efficacy and mechanism-of-action evaluations.

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Implication

In vitro study demonstrates progressive fibrosis and lipid accumulation in a human 3D liver model, highlighting its preclinical utility for drug evaluation.

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Maekawa et al. (2026) studied this question.

synapsesocial.com/papers/6a993503636c6408cfa7cbe7 https://doi.org/10.1254/fpj.26027

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A novel human 3D steatohepatitis model recapitulating disease progression for evaluating the efficacy and mechanism of action of MASH therapeutics

Key Points

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Implication

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Discussion

Cite This Study

A novel human 3D steatohepatitis model recapitulating disease progression for evaluating the efficacy and mechanism of action of MASH therapeutics

Key Points

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Implication

Abstract

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